The major objective of this project will be to correlate aging with homeostatic malfunctions involving oxidative metabolism in mammalian brain. We will address ourselves to two major problems: (1) the bioelectric and metabolic function of the intact brain; and (2) the basis for small changes in the energy balance, i.e. PC, ATP, ADP, and AMP of brain tissue at a time when serious neurological dysfunction is evident, e.g. abnormal EEG patterns. In our studies we will confront these two challenges directly. (1) We will apply unique optical monitoring techniques to measure very subtle and rapid shifts in on-going metabolism in the exposed but otherwise undisturbed, functioning cerebral cortex. (2) In our biochemical analyses we will stress the importance of alterations in metabolic flux rather than the concept that changes in metabolite concentrations are responsible for accompanying brain impairment during aging. These data will be correlated with age resulting from physiologic and biochemical perturbations of the tissue. Biochemical experiments will be done in vitro on tissue samples derived from the in vivo experiments.